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Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)

Primary Purpose

Gastro-Intestinal Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
5-FU
Leucovorin
5-FU
Irinotecan
Brivanib
Brivanib
Brivanib
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastro-Intestinal Cancer focused on measuring Gastro-Intestinal Cancer, NOS

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Histological/cytological confirmed diagnosis of Gastrointestinal malignancy, except pancreatic cancer
  • Eligible for 5FU/LV or FOLFIRI chemotherapy
  • ECOG 0-1
  • Able to swallow and tolerate tablets
  • Life expectancy of 3 months

Exclusion Criteria:

  • Unwilling to use acceptable method to avoid pregnancy of partner/self for the entire study period and up to 4 weeks after last dose
  • Women who are pregnant or breastfeeding
  • Pancreatic cancer
  • Known brain metastasis, evidence of leptomeningeal disease
  • History of thrombo-embolic disease
  • Hemorrhage/bleeding events
  • Uncontrolled or significant cardiovascular disease
  • Any 3 or more of the following risk factors: arterial thrombosis , smoking, hypercholesterolemia, hypertension, obesity (BMS>30) and diabetes
  • Pre-existing thyroid abnormality, not maintained with medication
  • QTC (Fridericia) >450 msec on two consecutive ECG's
  • Subjects with concomitant second malignancies ( except adequately treated non-melanoma skin, in situ carcinoma of bladder, cervix or breast, early prostate cancer)
  • Any major surgery within 4 weeks of study drug administration
  • Increased levels of both D-Dimer and Prothrombin fragment 1 +2
  • Arm B and C only-positive UGT1A1 genotype of TA7/TA7
  • History of allergy of brivanib or drug class
  • History of severe reactions to fluoropyrimidine therapy or irinotecan
  • Prior therapy with brivanib

Sites / Locations

  • Usc/Norris Comprehensive Cancer Center
  • Texas Oncology
  • Scott & White Memorial Hospital And Clinic
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm 1

Arm 2

Arm 3

Arm Description

Japanese Population

Outcomes

Primary Outcome Measures

Safety-Toxicity, evaluated according to NCI Common Terminology Criteria for Adverse Events v3.0. Assessments based on medical review of adverse events, results of vital signs, ECGs, echocardiography, physical examinations, and clinical laboratory tests

Secondary Outcome Measures

Pharmacokinetics (Cmax, Tmax, AUC (TAU), T-HALF) plasma concentration vs time for brivanib given alone and in combination with FOLFIRI. Individual concentrations (C) of 5FU will be calculated from samples on Day 2 in the presence and absence of Brivanib
Efficacy-Tumor BOR determined for treated subjects by radiological responses assessed by CT scan or MRI, by RECIST criteria (v1.1). Radiological tumor assessments to evaluate response & progression will be done every 8 wks or more frequently if indicated
Exploratory Measures (Biomarkers for Predictive Analysis): Potential predictive markers, including activity of FGF, VEGF and related pathways as well as K-RAS mutation status, will be evaluated based on blood or tumor samples

Full Information

First Posted
January 11, 2010
Last Updated
September 15, 2014
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT01046864
Brief Title
Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)
Official Title
A Phase Ib Multiple Ascending Dose Study to Evaluate the Safety of Brivanib in Combination With 5-Fluorouracil/Leucovorin (5FU/LV) and Brivanib in Combination With 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI) in Subjects With Advanced or Metastatic Gastrointestinal Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine a safe and maximum tolerable dose of Brivanib when combined with standard dose 5FU/LV and FOLFIRI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastro-Intestinal Cancer
Keywords
Gastro-Intestinal Cancer, NOS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Title
Arm 2
Arm Type
Experimental
Arm Title
Arm 3
Arm Type
Experimental
Arm Description
Japanese Population
Intervention Type
Drug
Intervention Name(s)
5-FU
Other Intervention Name(s)
Fluorouracil
Intervention Description
IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Folinic acid
Intervention Description
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
Intervention Type
Drug
Intervention Name(s)
5-FU
Other Intervention Name(s)
Fluorouracil
Intervention Description
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Intervention Description
IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
Intervention Type
Drug
Intervention Name(s)
Brivanib
Intervention Description
Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity
Intervention Type
Drug
Intervention Name(s)
Brivanib
Other Intervention Name(s)
BMS-582664
Intervention Description
Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity
Intervention Type
Drug
Intervention Name(s)
Brivanib
Other Intervention Name(s)
BMS-582664
Intervention Description
Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity
Primary Outcome Measure Information:
Title
Safety-Toxicity, evaluated according to NCI Common Terminology Criteria for Adverse Events v3.0. Assessments based on medical review of adverse events, results of vital signs, ECGs, echocardiography, physical examinations, and clinical laboratory tests
Time Frame
Cycle 4, Day 1
Secondary Outcome Measure Information:
Title
Pharmacokinetics (Cmax, Tmax, AUC (TAU), T-HALF) plasma concentration vs time for brivanib given alone and in combination with FOLFIRI. Individual concentrations (C) of 5FU will be calculated from samples on Day 2 in the presence and absence of Brivanib
Time Frame
Cycle 2, Day 2
Title
Efficacy-Tumor BOR determined for treated subjects by radiological responses assessed by CT scan or MRI, by RECIST criteria (v1.1). Radiological tumor assessments to evaluate response & progression will be done every 8 wks or more frequently if indicated
Time Frame
Every 8 weeks
Title
Exploratory Measures (Biomarkers for Predictive Analysis): Potential predictive markers, including activity of FGF, VEGF and related pathways as well as K-RAS mutation status, will be evaluated based on blood or tumor samples
Time Frame
Cycle 1, Cycle 2, every other cycle

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Histological/cytological confirmed diagnosis of Gastrointestinal malignancy, except pancreatic cancer Eligible for 5FU/LV or FOLFIRI chemotherapy ECOG 0-1 Able to swallow and tolerate tablets Life expectancy of 3 months Exclusion Criteria: Unwilling to use acceptable method to avoid pregnancy of partner/self for the entire study period and up to 4 weeks after last dose Women who are pregnant or breastfeeding Pancreatic cancer Known brain metastasis, evidence of leptomeningeal disease History of thrombo-embolic disease Hemorrhage/bleeding events Uncontrolled or significant cardiovascular disease Any 3 or more of the following risk factors: arterial thrombosis , smoking, hypercholesterolemia, hypertension, obesity (BMS>30) and diabetes Pre-existing thyroid abnormality, not maintained with medication QTC (Fridericia) >450 msec on two consecutive ECG's Subjects with concomitant second malignancies ( except adequately treated non-melanoma skin, in situ carcinoma of bladder, cervix or breast, early prostate cancer) Any major surgery within 4 weeks of study drug administration Increased levels of both D-Dimer and Prothrombin fragment 1 +2 Arm B and C only-positive UGT1A1 genotype of TA7/TA7 History of allergy of brivanib or drug class History of severe reactions to fluoropyrimidine therapy or irinotecan Prior therapy with brivanib
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Usc/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Texas Oncology
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Scott & White Memorial Hospital And Clinic
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Local Institution
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Local Institution
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Local Institution
City
Villejuif Cedex
ZIP/Postal Code
94800
Country
France

12. IPD Sharing Statement

Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource

Learn more about this trial

Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)

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